
Site selection is a critical determinant of clinical trial success. This comprehensive guide outlines 73 key indicators that may signal potential issues with a clinical trial site. The framework addresses both FDA and EMA compliance requirements, providing sponsors and CROs with a thorough evaluation tool for global trial site selection. Often, these aspects are difficult to assess as documentation might be confidential (i.e., clinical studies sponsored by other companies). Nevertheless, it is crucial to have these aspects in mind when evaluating or re–assessing a clinical site’s performance.
Infrastructure and Physical Resources (1-10)
A site’s physical infrastructure must meet rigorous regulatory standards across jurisdictions. Non-compliance with FDA 21 CFR Parts 11, 50, 54, 56, and 312 or EMA Clinical Trial Regulations can severely impact study integrity.
- Inadequate secure storage for investigational products (non-compliant with FDA 21 CFR Part 312 or EMA Guidelines on IMPs)
- Lack of temperature-controlled storage facilities with 24/7 monitoring and alarm systems (in case of an electronic system, this needs to be validated)
- Limited space for monitoring visits, audits, and regulatory inspections
- Insufficient private areas for patient consultations per ICH GCP
- Outdated laboratory equipment lacking current documented calibration processes and certificates
- Absence of backup power systems (Uninterrupted Power Supply, UPS) for critical equipment and systems
- Unreliable internet connectivity compromising EDC and other system access
- Inadequate specimen processing facilities per CAP/CLIA requirements
- Limited access to emergency equipment required by regional regulations
- Insufficient archived document storage space for extended retention periods
Staff Capabilities and Resources (11-20)
The human element in clinical research requires specific qualifications, training, and experience in regulatory requirements and GCP standards.
- High coordinator turnover rate
- Principal Investigator overcommitted (>3-4 active studies simultaneously)
- Lack of GCP-trained and adequately qualified backup personnel for critical roles
- Insufficient research pharmacy staff per protocol requirements
- No dedicated quality assurance personnel for site oversight, depending on local requirements
- Limited bilingual staff in culturally diverse areas
- Inadequate 24/7 coverage for study-specific procedures
- Absence of certified clinical research coordinators/study nurses
- Missing role-specific training documentation
- Missing documented evidence of PI supervision / Oversight
Operational Track Record (21-30)
Past performance across regulatory jurisdictions provides crucial insights into a site’s operational capabilities. The quoted figures might be difficult to assess, but former experience with the site might give hints.
- History of serious protocol deviations (>5% in previous studies)
- Poor enrollment performance (<50% of target in past trials)
- Multiple regulatory authority findings (FDA 483s/EMA inspection findings)
- Delayed query resolution (>30 days average response time)
- Pattern of missing regulatory submission deadlines (if applicable)
- Subject retention rates below 80% in previous trials
- Inconsistent source documentation practices
- Late safety reporting to sponsors or regulatory authorities (as applicable)
- Repeated protocol violations in similarly designed studies
- Poor track record in meeting study timelines (EDC entries, query resolution)
Quality Management System (31-40)
A robust quality management system (QMS) is fundamental for sponsors for ensuring compliance with ICH GCP E6(R2) requirements. Depending on regional requirements, a QMS might be a requirement for study participation or (only) recommended.
- Outdated or missing SOPs for critical processes
- Lack of risk-based internal auditing procedures
- Inadequate document version control systems
- No structured training program for study staff
- Poor CAPA system implementation and tracking
- Missing quality metrics and KPI monitoring
- Inadequate investigational product accountability procedures
- Non-compliant equipment calibration programs
- Absence of risk-based monitoring preparations
Clinical Data Handling Practices (41-50)
Compliance with FDA 21 CFR Part 11 and EMA electronic data requirements demands robust data management systems. The quoted figures might be difficult to assess for new sites, but former experience with the site might give hints.
- Delayed data entry (>3-5 days from source document completion, depending on sponsor requirements)
- Poor query resolution rates (e.g., <80% within 10 days, depending on sponsor requirements)
- Inconsistency between source data and data entered into the EDC
- Non-validated site-specific electronic systems
- Missing data backup and disaster recovery procedures
- Inadequate EDC system experience among staff
- Inadequate handling of (electronic) patient reported outcome data (questionnaires, diaries)
- Inadequate data privacy measures (GDPR/HIPAA)
- Poor medical coding practices (as applicable)
Regulatory Compliance (51-60)
Adherence to FDA, EMA, and local regulatory requirements is non-negotiable for clinical trial success.
- History of regulatory non-compliance findings
- Incomplete regulatory files per ICH GCP requirements
- Missing or delayed IRB/EC correspondence (as regionally applicable)
- Poor safety reporting compliance history
- Inadequate informed consent processes and documentation thereof
- Non-compliant investigational product handling
- Missing or inadequately completed training records
- Poor essential document maintenance and archiving
Communication and Responsiveness (61-70)
Effective communication is crucial for successful study execution and regulatory compliance.
- Delayed responses to feasibility questionnaires (e.g., >5 days)
- Poor interdepartmental communication systems
- Limited experience with sponsor interactions
- Missing escalation procedures for critical issues
- Inadequate communication documentation practices
- Limited availability for team meetings/tele-or video-conferences
- Inconsistent study progress reporting to sponsor or IRB/IEC (as regionally applicable)
- Poor (remote) monitoring preparation
- No interaction with CRA/clinical monitor after monitoring visit
- Inadequate handling of issues identified during clinical monitoring
Financial and Administrative (71-73)
Sound financial and administrative practices ensure sustainable study operations.
- Unrealistic budget expectations for study requirements
- Incomplete financial disclosure documentation
- Inadequate budget tracking mechanisms
Conclusion
Thorough evaluation of these 75 indicators during site selection is crucial for clinical trial success. While some issues may be addressable through proper support and oversight, others represent fundamental problems that should preclude site selection. The key is to:
- Systematically assess each category
- Document findings comprehensively
- Evaluate risks objectively
- Make informed decisions based on aggregate findings
- Implement appropriate monitoring and support where needed
Remember: Addressing red flags during site selection is significantly more cost-effective than managing issues after study initiation. For global trials, ensuring compliance with both FDA and EMA requirements, along with local regulations, is essential for study success.